RNA interference (RNAi) is a natural mechanism involving specific down regulation of target gene expression by double-stranded short interfering RNA (siRNA) [1]. RNAi has increasingly become a well-established tool in functional genomics and in target screening and validation in vitro [2, 3]. More importantly, the development of siRNA-based drugs holds promise in finding therapies for complex diseases such as diabetes, cancer, and viral infections [4-7].
As for other forms of nucleic acids such as plasmid DNA (pDNA), poor serum stability, unfavorable pharmacokinetics in vivo, and inefficient cellular uptake remain the main challenges for successful gene silencing applications [8]. One strategy to partly overcome such problems is the use of chemically modified siRNAs that exhibit resistance to nuclease degradation as well as improved cellular uptake [9-11]. Another strategy involves the use of polycation-based siRNA formulations. For instance, cationic lipid-based formulations were shown to be effective for in vitro and in vivo delivery of siRNA [12-15]. In contrast, cationic polymers were initially considered unsuitable for oligonucleotides delivery [16]. However, recent studies have shown that cationic polymers such as polyethyleneimine (PEI), polyamidoamine (PAMAM) dendrimers and poly-L-lysine (PLL) can be used for siRNA delivery [17-19]. Contradictory accounts on the efficiency of cationic polymers as delivery systems for oligonucleotides were formulated and delivered under conditions optimized for pDNA. Furthermore, several reports have raised concerns about the in vivo toxicity of the above mentioned polycations, which may hamper their future clinical applications [20-22]. Therefore, the search for non-toxic, efficient vectors for siRNA delivery is motivated.